Comparison of hypothesized enzyme mechanisms for carbonic anhydrase, carboxypeptidase A, and liver alcohol dehydrogenase is to be made by electronic structure calculations. Ab initio methods (all electron, exact Hamiltonian) with an extended s,p plus a d-polarization basis is to be employed with configuration interaction added where needed. Solvation effects are to be treated by the reaction field scheme and the screening of protein surface charges is studied by several models. The proposed research continues our program of identifying the electronic role of active site residues and determining preferred chemical mechanisms in well-characterized enzymes. Previous work made notable progress on ribonuclease A, the serine proteinases and pepsin and the current proposal attempts the major step up to metallozymes. Many new high resolution x-ray crystallographic studies of heme and flavo-proteins have been reported and we propose to extend our study of the role of hydrogen bonds in setting redox potentials to those proteins. The number of well-resolved crystal structures for cytochromes is now sufficient to make a critical, quantitative test of the hydrogen bond hypothesis and this could signal a key advance in understanding the coupling ans switching mechanism carried out by proteins. Investigation of a novel suggestion for the mode of action of the Ca++ binding protein calmodulin is also proposed.